Background/Purpose: The application of biologic substances is subject to a risk to develop antibodies against these structures causing adverse events or loss of efficacy. For TNF blocking antibodies such as adalimumab a strong immunogenicity has been demonstrated which is associated with a formation of anti-drug antibodies. In numerous studies the frequency of anti-adalimumab (anti-ADL) antibodies has been described in detail. In our study we aimed to assess the persistence of anti-drug antibodies after termination of adalimumab (ADL) treatment.

Methods: Eighteen RA patients (16 female/ 2 male, mean age 53.1±8.2 years) treated with adalimumab for mean 23.4±17 months (range 4-74 months) were identified as anti-ADL antibody positive and were switched to another biological treatment, 5 patients were treated with another TNF inhibitor (4 with etanercept, 1 with golimumab), and 13 with a B-cell depleting therapy (rituximab). Patients were followed-up for at least two years to analyse the persistence of anti-ADL antibodies. For the determination of anti-ADL antibodies the Promonitor® -anti-ADL assay (Proteomika, Spain) was used according to the manufacturer’s instructions. The assay is designed as a bridging assay with a cut-off value of 10 AU/ml. For calculation of results the data analysis software (http://www.myassays.com) was used.

Results: After termination of adalimumab therapy the mean±SD level of anti-ADL antibodies was 491±713 AU/ml (in a range between 13 and >2000 AU/ml). Within the following two years anti-ADL antibody levels decreased significantly (p<0.05 t-test for paired samples). In 5 patients anti-ADL antibodies disappeared completely. However, 13 patients remained anti-ADL positive with a mean±SD level of 237±463 AU/ml (range 10 – 1801 AU/ml) two years after termination of ADL therapy. In eight patients a serokonversion was observed within a further follow-up with the last positive result for anti-ADL antibodies after mean 47 months (range 24-72 months). We did not find an influence of the current treatment on the persistence of anti-ADL antibodies. Even in patients receiving a B-cell directed therapy anti-ADL antibodies persisted for ≥ 24 months in 12 out of 15 patients. However, patients with persisting anti-ADL antibodies had been treated longer with ADL and had higher antibody levels after termination of therapy, with mean treatment duration of 25±17.8 months and 15.4±11.3 months and antibody levels of 652±781 AU/ml and 74±50.0 AU/ml after termination of therapy, in patients with persisting antibody levels and patients without anti-ADL antibodies after 2 years, respectively.

Conclusion: Our results clearly show that anti-adalimumab antibodies are stable and persist for several months or even years after termination of therapy. High antibody levels are not completely resolved by several courses of a B-cell depletion therapy. Supported by Pfizer Pharma GmbH Germany